Glucocorticoids are useful therapeutic agents in the treatment of pulmonary fibrosis and in various other inflamed connective tissue diseases. Although used in these fibrotic diseases, the exact molecular mechanism of action on collagen metabolism remains unknown. In this proposal, we have focused on the mechanism of the inhibitory effect of glucocorticoids on collagen synthesis. Although the decreased rate of collagen synthesis by glucocorticoids was initially thought to result from a non-selective inhibition of protein synthesis, recent data from this laboratory indicate a dose-related selective decrease of collagen synthesis. At both the nascent chain and tissue levels, collagen synthesis was decreased to a greater extent than noncollagen protein synthesis; thus indicating a selective reduction in collagen synthesis. The studies described in this proposal provide a molecular basis for the therapeutic use of synthetic glucocorticoids as inhibitors of collagen synthesis. Glucocorticoid therapy is used clinically in lung fibrosis, liver fibrosis, arthritis and in a variety of dermatological diseases. The selective decrease of collagen synthesis by glucocorticoids may be the biochemical basis for their usefulness in treating chronic inflammatory diseases since collagen synthesis constitutes a very significant biochemical manifestation of chronically inflamed tissues.